@article{c889ab16524341998e2e8dc65ce6fe36,
title = "Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers",
abstract = "Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.",
keywords = "C. difficile infection, antibiotics, live biotherapeutic product, metabolites, metagenomics, microbiome, pharmacology",
author = "Melissa Dsouza and Rajita Menon and Emily Crossette and Bhattarai, {Shakti K.} and Jessica Schneider and Kim, {Yun Gi} and Shilpa Reddy and Silvia Caballero and Cintia Felix and Louis Cornacchione and Jared Hendrickson and Watson, {Andrea R.} and Minot, {Samuel S.} and Nick Greenfield and Lisa Schopf and Rose Szabady and Juan Patarroyo and William Smith and Pratibha Harrison and Kuijper, {Ed J.} and Kelly, {Ciaran P.} and Bernat Olle and Dmitri Bobilev and Silber, {Jeffrey L.} and Vanni Bucci and Bruce Roberts and Jeremiah Faith and Norman, {Jason M.}",
note = "Funding Information: The clinical study was funded by Vedanta Biosciences Inc. Research reported in this publication was supported by the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) under award number 4500002475. CARB-X funding for this research is sponsored by the Cooperative Agreement Number IDSEP160030 from the Assistant Secretary for Preparedness and Response (ASPR)/Biomedical Advanced Research and Development Authority (BARDA) and by an award from the Wellcome Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders. V.B. is supported by Sponsored Research Agreement by Vedanta Biosciences. The authors thank Pranali Pathare, PhD of 3P Scientific Communications for providing medical writing support for the preclinical sections, which was funded by Vedanta Biosciences, Inc. (Cambridge, MA, USA) in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Conceptualization, M.D. R.M. J.S. Y.-G.K. L.S. R.S. E.J.K. C.P.K. D.B. B.R. J.F. and J.M.N.; software, S.S.M. and N.G.; formal analysis, M.D. R.M. E.C. S.K.B. J.H. A.R.W. and P.H.; investigation, J.S. Y.-G.K. S.R. S.C. C.F. L.C. J.P. and W.S.; resources, S.S.M. and N.G.; data curation, M.D. and R.M.; writing – original draft, M.D. R.M. E.C. S.K.B. N.G. V.B. J.F. and J.M.N.; writing – reviewing & editing, M.D. R.M. E.C. S.K.B. J.S. R.S. B.O. V.B. B.R. J.L.S. J.F. and J.M.N.; visualization, M.D. R.M. E.C. S.K.B. J.H. and J.M.N.; supervision, L.S. B.O. D.B. V.B. B.R. J.F. J.L.S. and J.M.N.; funding acquisition, B.O. R.M. S.R. E.C. S.C. J.H. C.F. L.C. A.R.W. J.L.S. B.O. and J.M.N. are employees of Vedanta Biosciences and have an equity interest in the company. Vedanta Biosciences holds patents related to this work. M.D. J.S. Y.-G.K. J.P. L.S. R.S. W.S. D.B. and B.R. were employees of Vedanta Biosciences and had an equity interest in the company at the time of their contribution. J.F. is a member of the scientific advisory board of Vedanta Biosciences and has an equity interest in the company. The authors vouch for the accuracy and completeness of the data and data analyses. This content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response. For studies involving human subjects, we worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Funding Information: The clinical study was funded by Vedanta Biosciences Inc. Research reported in this publication was supported by the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) under award number 4500002475 . CARB-X funding for this research is sponsored by the Cooperative Agreement Number IDSEP160030 from the Assistant Secretary for Preparedness and Response (ASPR)/ Biomedical Advanced Research and Development Authority (BARDA) and by an award from the Wellcome Trust . The content is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders. V.B. is supported by Sponsored Research Agreement by Vedanta Biosciences . The authors thank Pranali Pathare, PhD of 3P Scientific Communications for providing medical writing support for the preclinical sections, which was funded by Vedanta Biosciences, Inc. (Cambridge, MA, USA) in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = apr,
day = "13",
doi = "10.1016/j.chom.2022.03.016",
language = "English",
volume = "30",
pages = "583--598.e8",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "4",
}